Melatonin - what's all the fuss about?

David Kennaway, Senior Research Fellow/Senior Lecturer, Circadian Physiology Group, Department of Obstetrics and Gynaecology, University of Adelaide, Adelaide

Aust Prescr 1997;20:98

Melatonin is the new fad drug from the U.S.A. that everyone seems to be talking about. There are books about it, it has been discussed on talk shows, in `Newsweek' and other popular magazines.
What is it? Why are people taking it, and why is it not available freely outside the U.S.A.?

Melatonin is a hormone produced from the amino acid, tryptophan, via serotonin in the pineal gland. Its production is unique in that it is synthesised and secreted predominantly at night between
about 9 p.m. and 8 a.m. The control of the production occurs via interactions between the brain's biological timing centre (the suprachiasmatic nucleus of the hypothalamus) and retinally perceived
light. While melatonin secretion is high during night-time darkness, it is not produced during casual darkness during the day. Similarly, while it is secreted while we sleep, sleep is not a
prerequisite for its production and it is not produced during daytime sleep.

Melatonin was discovered almost 40 years ago and yet, despite intensive research, the function of the rhythmic production and secretion in humans is very poorly understood. The localisation of
receptors for the hormone in parts of the hypothalamus, including the suprachiasmatic nucleus, has led to the idea that melatonin is involved in modulating physiological rhythms. These rhythms
include the sleep/wake rhythm, temperature rhythm and some hormonal rhythms. For this reason, medical researchers are investigating the possible role of melatonin in patients with disorders of
circadian rhythmicity such as sleep-timing disorders (as opposed to maintenance disorders) and society-induced timing problems resulting from trans-meridian jet travel and shift work.

Those promoting the free and general use of melatonin in the U.S.A. have used unusual features of American law to have melatonin classed as a dietary supplement on the basis that it is found in
some plants, and traces are likely to be ingested in animal products. It cannot be prescribed in Australia and is not available as a foodstuff, although people are able to bring personal supplies
into the country. The popular culture of melatonin surrounds its sleep-promoting and suggested anti-ageing properties. Melatonin is indeed a very weak hypnotic which has been shown in controlled
studies to shorten the latency to sleep onset. Whilst there is some evidence suggesting that melatonin is not toxic acutely or chronically1,2, there
have been no studies on efficacy in the wider population and no systematic studies on drug interactions or contraindications in specific diseases.

Who really needs to supplement their own melatonin production? A feature of melatonin research in humans has been the enormous variability in circulating levels between subjects (as much as
10-fold). Despite the variability, there have been no reported clinical consequences of being a low melatonin secretor. For example, patients with high melatonin are just as likely to be poor
sleepers as those with low melatonin. Similarly, given this large inter-individual variability, there is no evidence that melatonin production in individuals decreases with age (i.e. the belief that
you should take melatonin to counter an age-related decrease). Thus, there is no such thing as hypomelatoninaemia!

Why should we worry about unrestricted melatonin? The answer is simple. We simply do not know enough yet about the function of melatonin produced by the pineal or about the toxicity of exogenous
melatonin to sanction self-prescribed, self-administration. Melatonin is intimately involved in the fine tuning of the body's biological timing system, but the long-term consequences of tampering
with this system on physical and psychological well-being remain to be determined.